Abstract

The FDA review leading to accelerated approval of carfilzomib is described. A single arm trial enrolled 266 patients with multiple myeloma refractory to the most recent therapy, and who had received prior treatment with bortezomib and an immunomodulatory agent (IMID). Patients received carfilzomib by intravenous (IV) infusion over 2 to 10 minutes at a dose of 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 of the 28 days of cycle 1, and at a dose of 27 mg/m2 on the same schedule in cycle 2 and subsequent cycles. The primary efficacy endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) using International Myeloma Working Group response criteria. The safety of carfilzomib was evaluated in 526 patients with multiple myeloma treated with various dosing regimens. The ORR was 23%. The median duration of response was 7.8 months. Most common adverse reactions associated with carfilzomib infusion were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and fever. Most common serious adverse events were pneumonia, acute renal failure, fever, and congestive heart failure. Infusion reactions to carfilzomib could be reduced by pre-treatment with dexamethasone and IV fluids. On July 20, 2012, FDA granted accelerated approval of carfilzomib for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an IMID and who have demonstrated disease progression while on therapy or within 60 days of completion of the last therapy.